Because the incidence of pyoderma gangrenosum (PG) is low, no prospective randomized controlled trials and only a few studies with case numbers of more than 15 patients have been published. To date no guidelines for treatment of PG have been established far. The aim of the study was to provide an evidence-based review of the literature and an evaluation of recommendations for PG treatment. We performed an electronic search using the PubMed database and the term "pyoderma-gangrenosum." Literature published in the English language during the past two decades was reviewed. All relevant studies that could be obtained regardless of the study design were evaluated for grades of recommendation and levels of evidence. Data on patient characteristics including severity of the disease, localization of lesions, associated diseases, and treatment procedures were abstracted and evaluated for therapeutic outcome. We conclude that therapeutic efficacy of systemic treatment with corticosteroids and cyclosporine is best documented in the literature for disseminated as well as for localized disease and should be considered first-line therapy. In cases that do not respond to this treatment, we recommend alternative therapeutic procedures (eg, systemic treatment with corticosteroids and mycophenolate mofetil; mycophenolate mofetil and cyclosporine; tacrolimus; infliximab; or plasmapheresis), considering additional factors including associated diseases.

Treatment recommendations for pyoderma gangrenosum: an evidence-based review of the literature based on more than 350 patients.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by painful, necrotic ulceration. It typically affects patients in the third to sixth decades of life, with almost equal incidence in men and women. PG occurs most frequently on the lower extremities. Five clinical variants are currently recognized: classic, bullous, pustular, vegetative, and peristomal types. Half of PG cases are seen in association with systemic disease. Mimickers include infection, vascular insufficiency ulcers, systemic vasculitides, autoimmune disease, cancer, and exogenous tissue injury, among others. PG is often a diagnosis of exclusion, as there are no specific laboratory or histopathologic findings to confirm the diagnosis. PG thus presents many clinical challenges: it is difficult to diagnose, is frequently misdiagnosed, and often requires a work-up for underlying systemic disease. Successful management of PG typically requires multiple modalities to reduce inflammation and optimize wound healing, in addition to treatment of any underlying diseases. Prednisone and cyclosporine have been mainstays of systemic treatment for PG, although increasing evidence supports the use of biologic therapies, such as tumor necrosis factor-a inhibitors, for refractory cases of PG. Here, we review the clinical presentation and pathophysiology of PG, as well as its associated conditions, diagnostic work-up, and management.

/pdf/etiology-and-management-of-pyoderma-gangrenosum-a-1yd8psn10f.pdf

Etiology and management of pyoderma gangrenosum: a comprehensive review.

Background
Vitiligo is a chronic skin disorder characterised by patchy loss of skin colour. Some people experience itching before the appearance of a new patch. It affects people of any age or ethnicity, more than half of whom develop it before the age of 20 years. There are two main types: generalised vitiligo, the common symmetrical form, and segmental, affecting only one side of the body. Around 1% of the world's population has vitiligo, a disease causing white patches on the skin. Several treatments are available. Some can restore pigment but none can cure the disease.

Objectives
To assess the effects of all therapeutic interventions used in the management of vitiligo.

Search methods
We updated our searches of the following databases to October 2013: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2013, Issue 10), MEDLINE, Embase, AMED, PsycINFO, CINAHL and LILACS. We also searched five trials databases, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).

Selection criteria
Randomised controlled trials (RCTs) assessing the effects of treatments for vitiligo.

Data collection and analysis
At least two review authors independently assessed study eligibility and methodological quality, and extracted data.

Main results
This update of the 2010 review includes 96 studies, 57 from the previous update and 39 new studies, totalling 4512 participants. Most of the studies, covering a wide range of interventions, had fewer than 50 participants. All of the studies assessed repigmentation, however only five reported on all of our three primary outcomes which were quality of life, > 75% repigmentation and adverse effects. Of our secondary outcomes, six studies measured cessation of spread but none assessed long-term permanence of repigmentation resulting from treatment at two years follow-up.

Most of the studies assessed combination therapies which generally reported better results. New interventions include seven new surgical interventions.

We analysed the data from 25 studies which assessed our primary outcomes. We used the effect measures risk ratio (RR), and odds ratio (OR) with their 95% confidence intervals (CI) and where N is the number of participants in the study.

We were only able to analyse one of nine studies assessing quality of life and this showed no statistically significant improvement between the comparators.

Nine analyses from eight studies reported >75% repigmentation. In the following studies the repigmentation was better in the combination therapy group: calcipotriol plus PUVA (psoralen with UVA light) versus PUVA (paired OR 4.25, 95% CI 1.43 to 12.64, one study, N = 27); hydrocortisone-17-butyrate plus excimer laser versus excimer laser alone (RR 2.57, 95% CI 1.20 to 5.50, one study, N = 84); oral minipulse of prednisolone (OMP) plus NB-UVB (narrowband UVB) versus OMP alone (RR 7.41, 95% CI 1.03 to 53.26, one study, N = 47); azathioprine with PUVA versus PUVA alone (RR 17.77, 95% CI 1.08 to 291.82, one study, N = 58) and 8-Methoxypsoralen (8-MOP ) plus sunlight versus psoralen (RR 2.50, 95% CI 1.06 to 5.91, one study, N = 168). In these three studies ginkgo biloba was better than placebo (RR 4.40, 95% CI 1.08 to 17.95, one study, N = 47); clobetasol propionate was better than PUVAsol (PUVA with sunlight) (RR 4.70, 95% CI 1.14 to 19.39, one study, N = 45); split skin grafts with PUVAsol was better than minipunch grafts with PUVAsol (RR 1.89, 95% CI 1.25 to 2.85, one study, N = 64).

We performed one meta-analysis of three studies, in which we found a non-significant 60% increase in the proportion of participants achieving >75% repigmentation in favour of NB-UVB compared to PUVA (RR 1.60, 95% CI 0.74 to 3.45; I² = 0%).

Studies assessing topical preparations, in particular topical corticosteroids, reported most adverse effects. However, in combination studies it was difficult to ascertain which treatment caused these effects. We performed two analyses from a pooled analysis of three studies on adverse effects. Where NB-UVB was compared to PUVA, the NB-UVB group reported less observations of nausea in three studies (RR 0.13, 95% CI 0.02 to 0.69; I² = 0% three studies, N = 156) and erythema in two studies (RR 0.73, 95% CI 0.55 to 0.98; I² = 0%, two studies, N = 106), but not itching in two studies (RR 0.57, 95% CI 0.20 to 1.60; I² = 0%, two studies, N = 106).

Very few studies only assessed children or included segmental vitiligo. We found one study of psychological interventions but we could not include the outcomes in our statistical analyses. We found no studies evaluating micropigmentation, depigmentation, or cosmetic camouflage.

Authors' conclusions
This review has found some evidence from individual studies to support existing therapies for vitiligo, but the usefulness of the findings is limited by the different designs and outcome measurements and lack of quality of life measures. There is a need for follow-up studies to assess permanence of repigmentation as well as high-quality randomised trials using standardised measures and which also address quality of life.

Interventions for vitiligo

Tumors of the epidermis

Systemic lupus erythematosus.

Background Pyoderma gangrenosum (PG) is an uncommon, destructive, cutaneous ulceration, belonging to the neutrophilic disease spectrum. It is associated with systemic disease in 50% of cases.



Methods We report a retrospective study of 21 cases of PG. All cases studied fulfilled the following criteria: (i) clinical features of PG; (ii) histopathology consistent with a diagnosis of PG, and excluding other specific dermatoses.



Results The average age of our patients was 41.8 years. The male to female ratio was 1.1. The typical ulcerative variant was found in 17 patients, bullous PG in two patients, and the granulomatous variant in two patients. Sixty-two per cent of our patients had lesions on their lower legs. Two patients had neutrophilic pulmonary involvement concurrent with the ulcers. An association with other internal diseases was noted in 12 patients. Histopathologic study showed vasculitis in 13 patients. Of these, 11 were leukocytoclastic and the others predominantly lymphocytic.



Conclusions PG is a rare disease, with the ulcerative variant being most frequent. The lower legs are the most commonly affected sites. The recurrence rate in our study was about 46% regardless of the treatment prescribed. Pulmonary involvement was fatal in two patients.

Pyoderma gangrenosum: a report of 21 cases

Trigeminal trophic syndrome, a rare cause of facial ulceration, is the consequence of damage to the trigeminal nerve or its central sensory connections. We report two cases of trigeminal trophic syndrome, complications of cerebral vascular accidents. A 65-year-old woman complained of numerous and progressive ulcers of the right side of her face of 2 month's duration. A 67-year-old woman presented with an ulcer of the ala nasi of 10 week's duration. This syndrome most commonly occurs in women with an average age of 57 years. About 100 cases are reported in the literature. The diagnosis is made on clinical grounds, and is suggested when loss of sensation occurs in association with unilateral facial ulceration, especially involving the ala nasi. Once the ulcers appear, they are extremely persistent.

Trigeminal trophic syndrome: a report of two cases with review of literature.

Despite prevention programs tuberculosis is still endemic in developing countries. We assessed the epidemiologic and clinical profiles of childhood cutaneous tuberculosis in our dermatology department from 1981 to 2000 and compared it to previous Tunisian reports and to the relevant literature. This is a retrospective study over a 20-year period (1981-2000) in a large teaching hospital of the capital. Patients included were below age 15 years. Diagnosis was based upon clinical examination tuberculin reaction histopathology and response to antitubercular therapy. There were 26 patients with cutaneous tuberculosis 0.1 percent of the total number of dermatology outpatients for that time period. Of these 26 seven (27 %) were immunocompetent. There were four boys and three girls and the mean age was 9.5 years. Three patients had lupus vulgaris three had scrofuloderma and one child had orificial tuberculosis. Six out of seven children were BCG vaccinated. There was no family history of tuberculosis. The Mantoux reaction was positive in six children. There was no systemic organ involvement in all cases. All patients were treated successfully with triple or quadruple anti-tubercular drugs for 4-11 months. Compared to a previous Tunisian report conducted over an 8-year period in the seventies the incidence of childhood cutaneous tuberculosis has decreased. In that report scrofuloderma was the most frequent form. Currently the incidence of lupus vulgaris has reached that of scrofuloderma demonstrating the increase of the clinical pattern associated with strong immunity. All children had localized disease and responded to antimycobcterial chemotherapy. (authors)

Childhood cutaneous tuberculosis: a 20-year retrospective study in Tunis.

Background Pemphigus is an autoimmune intraepidermal blistering disease mediated by autoantibodies targeting desmosomes. It can be induced by many triggers, such as ionizing radiation.



Methods  We report a case of radiotherapy-induced pemphigus (RIP) with a review of the published cases in the English and French literature.



Results  A 61-year old man was diagnosed to have epidermoid carcinoma of the piriform sinus and then received a 70 Gy radiation therapy. One month after the treatment completion, multiple blisters and erosions occurred initially on the site of irradiation, then in other skin areas. Histological examination showed an intraepidermal blister with acantholysis and necrosis of individual keratinocytes. Direct immunofluorescence and indirect immunofluorescence were typical of pemphigus. Immunoblot revealed antibodies reacting with a 110 kDa antigen. This feature was consistent with the diagnosis of RIP. Less than 20 cases of RIP have been reported previously. Mean age at diagnosis was 64.2 years, and there is a slight female preponderance. RIP occurred, in most cases, initially within the area of irradiation.



Conclusion  Our patient showed some distinctive findings never reported previously in RIP: a histological focal keratinocyte necrosis, and the presence of autoantibodies reacting with a 110 kDa keratinocytic protein in immunoblot analysis. Because of a different prognosis, it is important to differentiate RIP and paraneoplastic pemphigus (PNP), although cases of ionizing radiation-induced PNP had also been described. As in our patient, RIP seems to respond well to systemic corticosteroids and immunosuppressive therapy, which induce remission within a few months.

Samy Fenniche

Papers

Pyoderma gangrenosum: a report of 21 cases

Trigeminal trophic syndrome: a report of two cases with review of literature.

Childhood cutaneous tuberculosis: a 20-year retrospective study in Tunis.

Radiotherapy-induced pemphigus vulgaris with autoantibodies targeting a 110 kDa epidermal antigen.

Morphea profunda in a young infant after hepatitis B vaccination